title: Non-epithelial stem cells and cortical interneuron production in the human ganglionic eminences.
abstract: GABAergic cortical interneurons underlie the complexity of neural circuits and are particularly numerous and diverse in humans. In rodents, cortical interneurons originate in the subpallial ganglionic eminences, but their developmental origins in humans are controversial. We characterized the developing human ganglionic eminences and found that the subventricular zone (SVZ) expanded massively during the early second trimester, becoming densely populated with neural stem cells and intermediate progenitor cells. In contrast with the cortex, most stem cells in the ganglionic eminence SVZ did not maintain radial fibers or orientation. The medial ganglionic eminence exhibited unique patterns of progenitor cell organization and clustering, and markers revealed that the caudal ganglionic eminence generated a greater proportion of cortical interneurons in humans than in rodents. On the basis of labeling of newborn neurons in slice culture and mapping of proliferating interneuron progenitors, we conclude that the vast majority of human cortical interneurons are produced in the ganglionic eminences, including an enormous contribution from non-epithelial SVZ stem cells.
authors.affiliation: 1] Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, California, USA. [2] Department of Neurology, University of California, San Francisco, San Francisco, California, USA. [3].
authors.forename: David V
authors.initials: DV
authors.lastname: Hansen
authors.forename: Jan H
authors.initials: JH
authors.lastname: Lui
authors.forename: Pierre
authors.initials: P
authors.lastname: Flandin
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: John L
authors.initials: JL
authors.lastname: Rubenstein
authors.forename: Arturo
authors.initials: A
authors.lastname: Alvarez-Buylla
authors.forename: Arnold R
authors.initials: AR
authors.lastname: Kriegstein
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D002552:Cerebral Ventricles / Q000166:cytology*; D005333:Fetus; D059330:GABAergic Neurons / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D007395:Interneurons / Q000502:physiology*; D060850:LIM-Homeodomain Proteins / Q000378:metabolism; D051379:Mice; D039902:Multipotent Stem Cells / Q000502:physiology*; D019579:Neocortex / Q000033:anatomy & histology / Q000196:embryology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C121947:LHX6 protein, human; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D014157:Transcription Factors